[Hematopoietic factors: serum concentrations and clinical application].
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Erythropoietin↗
Biomedical subjects
S Iki
Publications and source records attributed to S Iki.
Serum thrombopoietin level in various hematological diseases.
To investigate the pathophysiological role of thrombopoietin (TPO) in thrombopoiesis, we measured its serum levels in 15 healthy individuals, 84 patients with various hematological diseases and 2 patients with liver cirrhosis using an enzyme immunoassay procedure. The TPO level was 0.84 +/- 0.40 f mol/ml in normal individuals. TPO levels were considerably elevated in patients with myelosuppression after intensification chemotherapy of acute leukemia in complete remission (postchemotherapy group; n = 18; 18.46 +/- 9.70 f mol/ml). When the data of normal individuals and the postchemotherapy group were combined, TPO levels were inversely correlated with the platelet count in this combined group. We compared these data of normal individuals and the postchemotherapy group with various hematological disease states. In aplastic anemia (n = 13; 16.03 +/- 9.44 f mol/ml), acute lymphoblastic leukemia (n = 5; 10.36 +/- 5.57 f mol/ml), malignant lymphoma (n = 6; 2.79 +/- 2.27 f mol/ml), multiple myeloma (n = 3; 3.34 +/- 0.20 f mol/ml) and chronic lymphocytic leukemia (n = 2; 1.71 +/- 3.91 f mol/ml), the relationship of serum TPO levels and platelet counts was almost the same as in the combined group with normal individuals and the postchemotherapy group. However, the TPO levels were slightly higher in myeloproliferative disorders (n = 12; 1.99 +/- 1.47 f mol/ml) and lower in acute myelogenous leukemia (n = 8; 2.27 +/- 1.25 f mol/ml), hypoplastic leukemia (n = 3; 2.76 +/- 2.23 f mol/ml), myelodysplastic syndrome (n = 2; 0.42 +/- 0.60 f mol/ml), liver cirrhosis (n = 2; 1.50 +/- 0.92 f mol/ml) and idiopathic thrombocytopenic purpura (n = 12; 2.08 +/- 1.41 f mol/ml), when compared to the regression line for the combined group with normal individuals and postchemotherapy group. These findings suggest that TPO might play an important role in regulation of the platelet count in normal and pathological conditions.
Adult↗
Pharmacokinetics of all-trans-retinoic acid in Japanese patients with acute promyelocytic leukemia.
All-trans-retinoic acid (ATRA) was administered at 45 mg/m2 to 4 Japanese patients with acute promyelocytic leukemia (APL). A pharmacokinetic study revealed that the mean peak plasma concentration was 208 ng/ml and was reached at 150 min after ingestion. The mean area under the concentration x time curve (AUC) was 498 ng.h/ml. Two patients showed a good hematological response to ATRA, and they had higher peak plasma concentrations of ATRA and larger AUCs. In one patient, dose escalation of ATRA (90 mg/m2) increased the plasma concentration markedly. In another patient, the plasma concentration decreased markedly in the fasting state. A larger pharmacokinetic study is necessary to examine the influence of food on the absorption of this agent and an optimum administration schedule of ATRA in Japanese APL cases.
Adult↗
Administration of granulocyte colony-stimulating factor during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia.
Granulocyte colony-stimulating factor (G-CSF) enhances the differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA) in vitro. Accordingly, we initiated a pilot study on G-CSF in APL patients who developed neutropenia and severe infection during remission induction therapy with ATRA. Seven out of nine treated patients displayed a marked increase in granulocyte counts without leukemic regrowth, and two displayed a dramatic decrease in leukemic blasts. However, leukemic regrowth occurred in two patients under treatment for post-ATRA relapse. Our findings suggest that administration of G-CSF combined with ATRA can improve the hematological state in APL patients not previously receiving ATRA therapy.
Adult↗
CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with partial deletion of the long arm of chromosome 16.
Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.
Amino Acid Sequence↗
[Adult T-cell leukemia with diffuse panbronchiolitis-like lung infiltration].
A 46-year old man was admitted complaining of dyspnea. Physical examination revealed superficial lymph nodes swelling, and coarse crackles over the lung. Chest X-ray film showed diffuse small granular shadows, suggesting diffuse panbronchiolitis (DPB). Peripheral blood smears showed cells with flower like nuclei. HTLV-I antibody was positive in the serum. He was diagnosed as having adult T-cell leukemia (ATL). Transbronchial lung biopsy showed diffuse infiltration of mononuclear cells around bronchioalveoli. The mononuclear cells stained positively for Pan T, CD2, CD3, CD4, CD5, CD25, and DNA from the cells showed HTLV-I provirus monoclonal integration. This is a rare case of ATL accompanied by DPB-like bronchioalveolar ATL cell infiltration.
Antigens, CD↗
Tyrosine phosphorylation of vav protooncogene product in primary human myelogenous leukemic cells stimulated by granulocyte colony-stimulating factor.
Granulocyte colony-stimulating factor(G-CSF), but not granulocyte-macrophage CSF(GM-CSF), induced tyrosine phosphorylation of 95-kDa protein in 13 cases of primary human acute myelogenous leukemic cells. Electrophoretic mobility of 95-kDa phosphoprotein and the protooncogene product p95vav was identical. In addition, p95vav was tyrosine-phosphorylated only in G-CSF-stimulated cells. In contrast to primary leukemic cells, amount of p95vav was under detectable level and G-CSF did not induce tyrosine phosphorylation of 90-100-kDa proteins in human neutrophils. These results indicate specific involvement of vav product in signaling pathway of G-CSF in primary human leukemic cells.
Amino Acid Sequence↗
Granulocyte colony-stimulating factor in acute myeloid leukemia.
The clinical application of recombinant human G-CSF in patients with acute myeloid leukemia (AML) has been controversial because it stimulates the in vitro proliferation of leukemic cells. In order to explore the possibility of predicting in vivo leukemic proliferation after G-CSF administration to AML patients by using in vitro assays, we investigated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia following chemotherapy (G-CSF group) and 16 patients who did not (control group). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, while 11 of the 16 control patients developed leukemic resurgence. In the G-CSF group, the frequency of leukemic resurgence among patients whose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there were no significant differences between the G-CSF and control groups in [3H]thymidine incorporation by leukemic cells and leukemic colony formation after the addition of G-CSF to cultures. The G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 pM, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurgence occurred (200 in the G-CSF group and 260 in the control group) than when it did not (3400 and 3030, respectively). Immunophenotyping (for CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between blasts from the patients with and without leukemic resurgence in the G-CSF group. Thus, we conclude that the in vivo leukemic resurgence during G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine or with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptors with a high affinity irrespective of whether patients receive G-CSF.
Acute Disease↗
Combination therapy with granulocyte colony-stimulating factor, all-trans retinoic acid, and low-dose cytotoxic drugs for acute myelogenous leukemia.
A 67-year-old man presented with acute myelogenous leukemia (M2). Peripheral blood examination revealed a leukocyte count of 1,700/mu l with 1% myeloblasts, and bone marrow aspiration showed 42.6% myeloblasts with Auer bodies. Culture of his marrow cells at diagnosis showed that granulocyte colony-stimulating factor (G-CSF) promoted cell proliferation, while all-trans retinoic acid (ATRA) inhibited the proliferative effect of G-CSF and induced differentiation. Combination therapy with G-CSF, ATRA, and low-dose cytotoxic drugs achieved complete remission without severe marrow suppression.
Aged↗
[Acute promyelocytic leukemia (APL) resulting in broad cerebral infarction during all-trans retinoic acid (ATRA) treatment].
A 27-year-old woman visited Kanto Teishin Hospital complaining of fever and petechiae in September, 1992. Her fetus had suddenly died in the uterus two weeks before (in the sixth month of pregnancy). Total white blood cell (WBC) count was 3.2 x 10(3)/microliters with 80% promyelocytes. Bone marrow was hypercellular with 90% promyelocytes. Disseminated intravascular coagulation (DIC) was recognized. She was diagnosed as having acute promyelocytic leukemia (APL), and treatment with daily oral administration of all-trans retinoic acid (ATRA) (70 mg/body/day) was begun. On day 4, hemiplegia and aphasia appeared. Broad cerebral infarction was suspected from computed tomography. On day 9, the WBC count increased rapidly, standard chemotherapy was added and she achieved complete remission. ATRA is known to have stimulatory effects on the differentiation of APL cells, but some reports have described thromboembolic events during the administration of ATRA. In this case, ATRA might have affected coagulability resulting in cerebral infarction.
Adult↗
Cytotoxic drug-induced pneumonia and possible augmentation by G-CSF--clinical attention.
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Adult↗
[Improvement of anemia by recombinant human erythropoietin in paroxysmal nocturnal hemoglobinuria].
A 32-year-old man visited Kanto Teishin Hospital complaining of general fatigue in May, 1992. He had been diagnosed as having paroxysmal nocturnal hemoglobinuria since 1980, because of brownish urine in the morning. He received blood transfusion in 1980. In 1983, he was treated with medication. There was no remarkable improvement, however, and he stopped coming to the hospital. When he was admitted to our hospital, hemolytic anemia and hemosiderinuria were noticed. Sucrose hemolysis test and acidified-serum lysis test (Ham test) were both positive. Positive rates of decay accelerating factor and CD59 were 38.8% (control 100%) and 45.4% (control 100%), respectively. His diagnosis was thus confirmed. Bone marrow was slightly hypocellular, and erythroid cells were relatively hyperplastic (M/E ratio 0.68). The oral administration of iron and oxymetholone was not effective for anemia. He was treated with daily subcutaneous administration of recombinant human erythropoietin (EPO, 3,000U/body/day). His hemoglobin level increased from 7.5g/dl to 12.0g/dl in 4 weeks, and general fatigue disappeared. Since he had concurrent chronic hepatitis C, alpha-interferon was also administered and his hemoglobin level is now controlled between 10 and 11g/dl. This case suggests that EPO can be useful for treating hemolytic anemia, even though erythroid cells in the bone marrow are hyperplastic.
Adult↗
Serum erythropoietin titers in hematological malignancies and related diseases.
Serum erythropoietin (Epo) titers in patients with various hematological malignancies and related diseases were determined by radioimmunoassay. Serum Epo titer was inversely correlated with hemoglobin concentration in iron deficiency anemia, aplastic anemia, myelodysplastic syndromes (MDS), acute leukemia, malignant lymphoma, multiple myeloma and myelofibrosis, but there was no correlation between serum Epo titer and hemoglobin concentration in chronic myelogenous leukemia or polycythemias. Serum Epo titers in aplastic anemia were much higher than those in iron deficiency anemia. Serum Epo titers in MDS, malignant lymphoma and multiple myeloma differed considerably among patients. Serum Epo titers in untreated polycythemia vera were significantly lower than in treated polycythemia vera or secondary polycythemia.
Anemia↗
[Changes in bone marrow MRI patterns in aplastic anemia before and after successful treatment with ATG].
In order to evaluate the usefulness of MRI in estimating bone marrow cellularity, we performed MRI of the lumbar spine in two patients with severe aplastic anemia, before and after successful treatment with antithymocyte globulin (ATG). Case 1, a 25-year-old man with idiopathic aplastic anemia, was treated with ATG 6 months after the onset. One month after treatment, his peripheral blood count and bone marrow cellularity recovered, and the MRI bone marrow pattern became normal. Case 2, a 78-year-old woman with drug-induced aplastic anemia, was treated with ATG 4 months after the onset. Three months after treatment, her peripheral blood count improved. Five months after treatment, her bone marrow cellularity recovered and the MRI bone marrow pattern was normal for her age. Seven months after treatment, when her peripheral blood count was almost normal, we observed hypercellular bone marrow restoration at the periphery of the vertebrae. MRI seems to be an effective method of evaluating bone marrow recovery in aplastic anemia.
Adult↗
[Immunoblastic lymphadenopathy-like T cell lymphoma accompanied by autoimmune hemolytic anemia].
A 62-year-old man was admitted to our hospital because of generalized lymphadenopathy, fever and skin eruptions. The histology of the right cervical lymph nodes showed immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. His laboratory data were as follows: hemoglobin concentration 7.1 g/dl, red blood cells 1,850,000/microliters, reticulocytes 4.2%, total bilirubin 2.6mg/dl, direct bilirubin 0.5mg/dl, haptoglobin less than 10mg/dl, positive Coombs test. He was diagnosed as having IBL-like T cell lymphoma accompanied by autoimmune hemolytic anemia. He was successfully treated with combination chemotherapy (Pro-MACE), and lymph node swelling and hemolytic anemia disappeared. He has been in complete remission for more than 1 year.
Anemia, Hemolytic, Autoimmune↗
[alpha-Interferon in the treatment of essential thrombocythemia].
Two patients with essential thrombocythemia were successfully treated by administering native alpha-interferon (alpha-IFN). One patient was a 38-year-old man in whom thrombocytosis was found accidentally. His platelet count on admission was 880,000/microliters and megakaryocytes increased. Three million units of alpha-IFN was administered subcutaneously everyday, and the platelet count decreased gradually to about 500,000/microliters within 2 weeks. The other patient was a 66-year-old woman who visited our hospital complaining of tenderness and swelling of the fingertips. Her platelet count was 1,610,000/microliters, and megakaryocytes increased and showed abnormal morphology. Six million units of alpha-IFN was administered subcutaneously every other day. The tenderness and swelling of the fingertips disappeared soon after the beginning of alpha-IFN administration. The platelet count decreased to about 500,000/microliters within 10 days, but she developed itching of the skin over the entire body. Therefore, alpha-IFN treatment was discontinued. It was suggested that alpha-IFN suppresses not only the maturation and proliferation of the progenitors of megakaryocytes but also the production of platelets from megakaryocytes. Administration of alpha-IFN should be considered in treating patients with essential thrombocythemia, because effects appear soon and alpha-IFN does not induce a second malignancy.
Adult↗
Adverse effect of erythropoietin in myeloproliferative disorders.
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Aged↗
Interleukin-6-producing pheochromocytoma.
A 42-year-old female with high fever and headache was admitted. Physical examination revealed hypertension, thrombocytosis with megakaryocytosis, hyperfibrinogenemia, and high level of serum noradrenaline. After operation of extramedullary pheochromocytoma, all symptoms disappeared and findings became normal. The supernatant of tumor culture showed high levels of interleukin-6.
Adrenal Gland Neoplasms↗